The present invention is directed to a pharmaceutical composition containing refined detoxified endotoxin (RDE) in combination with a pyridine-soluble extract of a microorganism (PE). The RDE used in the present composition is characterized as having no detectable 2-keto-3-deoxyoctanoate, between about 350 and 475 nmoles/mg of phosphorus and between about 1700 and 2000 nmoles/mg of fatty acids. The PE contains between about 3 and 20% by weight of protein, about 10 to 40% by weight of sugar, and about 35 to 60% by weight of fatty acids. The composition is effective to obtain remission and/or regression of cancerous tumors in warm-blooded animals.
Bacteria such as Corynebacterium parvum have been the subject of experimental work to isolate and characterize the component responsible for inducing inhibition of tumor growth [see for example, Anti Tumor Activity and Lymphoreticular Stimulation Properties of Fractions Isolated from C. parvum; Cantrell, et al, Cancer Research 39, pgs. 3554-3563 (September, 1979)]. Apart from anti-tumor activity, C. parvum is a potent stimulator of the lymphoreticular system resulting in undesirable increases in spleen and liver weights and blastogenesis. It has been discovered that a pyridine-soluble extract of a microorganism such as C. parvum possesses potent anti-tumor properties without the undesirable toxic effects associated with the prior art products.
Endotoxic extracts obtained from Enterobacteriaciae including parent organisms and mutants are known. These extracts have been used for immunotherapy of various immunogenic tumors [see, Peptides as Requirement for Immunotherapy of the Guinea-Pig Line-10 Tumor with Endotoxins; Ribi, et al, Cancer Immunol. Immunother. Vol. 7, pgs. 43-58 (1979) incorporated herein by reference]. However, the endotoxin extracts are known to be highly toxic and, therefore, of limited use in the treatment of cancerous tumors. Efforts have been made to "detoxify" the endotoxins while retaining its tumor regressive capacity. As shown in Ribi, et al, chemical procedures known to detoxify endotoxins while retaining adjuvanticity, such as succinylation and phthalylation resulted in both loss of endotoxicity and tumor regressive potency. Therefore, prior art attempts to obtain an endotoxin product having high tumor regressive potency and little or no toxicity have thus far not been successful.